Mutational analyses ofBRCA1 andBRCA2 in Ashkenazi and non-Ashkenazi Jewish women with familial breast and ovarian cancer

Autor: Revital Bruchim Bar Sade, Limor Green, Samario Haitchick, Eitan Friedman, Peter J. Oefner, Anna Kruglikova, Efrat Dagan, Robert M.W. Hofstra, Rizel S, Ruth Gershoni Baruch, Inge M. Mulder, Ronit Shiri-Sverdlov, Ziad Abdeen, Boleslaw Goldman, Moshe Z. Papa, Teresa Wagner
Rok vydání: 2000
Předmět:
Zdroj: Human Mutation. 16:491-501
ISSN: 1098-1004
1059-7794
Popis: In Ashkenazi (East European) Jews, three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174-delT) account for the majority of germline mutations in high risk breast and/or ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG, Tyr978Ter, and a handful of "private" mutations have been reported anecdotally within both genes. In this study we attempted to determine the spectrum of BRCA1 and BRCA2 mutations in high-risk Jewish individuals, non-carriers of any of the predominant Jewish mutations. We employed multiplex PCR and denaturing gradient gel electrophoresis (DGGE) analysis for BRCA2, and combined denaturing high performance liquid chromatography (DHPLC) and protein truncation rest (PTT) for BRCA1, complemented by DNA sequencing. We screened 47 high-risk Jewish individuals, 26 Ashkenazis, and 21 non-Ashkenazis. Overall, 13 sequence alterations in BRCA1 and eight in BRCA2 were detected: nine neutral polymorphisms and 12 missense mutations, including five novel ones. The novel missense mutations did not co-segregate with disease in BRCA1 and were detected at rates of 6.25% to 52.5% in the general population for BRCA2, Our findings suggest that except for the predominant mutations in BRCA1 and BRCA2 in Jewish individuals, there are only a handful of pathogenic mutations within these genes. It may imply novel genes may underlie inherited susceptibility to breast/ovarian cancer in Jewish individuals. Hum Mutat 16:491-501, 2000. (C) 2000 Wiley-Liss, Inc.
Databáze: OpenAIRE
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